Acute phenytoin toxicity followed by seizure breakthrough from a ticlopidine-phenytoin interaction

To review a case of a drug-drug interaction between phenytoin sodium and ticlopidine hydrochloride that resulted in acute phenytoin toxicity and permanent memory loss.

A 63-year-old man who was maintained with a stable dose of phenytoin for treatment of seizures began treatment with ticlopidine following percutaneous transluminal angioplasty and stent placement. Within 3 weeks of beginning treatment with ticlopidine, he experienced acute clinical toxic effects of phenytoin with a maximum measured phenytoin concentration of 162.4 micromol/L. Phenytoin concentration decreased to 36 micromol/L after discontinuing treatment with ticlopidine and reducing the phenytoin dose. Subsequently, the patient developed probable complex partial status epilepticus.

Ticlopidine is a metabolic inhibitor of several drugs. Because of the potential for acute and permanent adverse effects from a drug-drug interaction, phenytoin concentrations should be carefully monitored when beginning or ending ticlopidine therapy.